March 2010




Exercising caution with prophylaxis

by Matt Young EyeWorld Contributing Editor

Material used for preparation of cefuroxime solution for injection into the anterior chamber.

Source: Bjorn Johansson, M.D.

When cefuroxime emerged as a serious form of cataract surgery prophylaxis, especially in Europe after positive study results from the European Society of Cataract and Refractive Surgeons were revealed, there were still plenty of skeptics. In the May 2007 issue of EyeWorld, Peter Barry, F.R.C.S., consultant ophthalmic surgeon, Royal Eye and Ear Hospital and St. Vincent’s Hospital, Dublin, Ireland, critiqued cefuroxime as “kitchen pharmacy.” “Cefuroxime is neither licensed nor commercially available for intraocular use,” Dr. Barry wrote. “While a physician can take responsibility for using it off-license, this requires the dilution of the 750 mg of powdered cefuroxime to a dilution of 1 mg in 0.1 ml and exposes the user to the risks of ‘kitchen’ pharmacy with potential errors of dilution, errors of diluent, possible induction of Toxic Anterior Segment Syndrome, and, frighteningly, possible contamination (e.g., by Pseudomonas), which is not sensitive to cefuroxime.”

Although Dr. Barry’s concerns remain credible, a new study suggests at least some dilution errors with cefuroxime may not be all that concerning. The study found that a major dilution error—3 mg in 0.1 mL concentration of cefuroxime (rather than the suggested dose of 1 mg per 0.1 mL)—caused no adverse events in six eyes of six patients. “No adverse reaction or inflammation was observed at postoperative examination,” according to lead study author Yasar Sakarya, M.D., Gozmer Eye Center, Denizli, Turkey. “All patients achieved 20/20 or better vision at the end of the first week.”

An error in the making

All six eyes were operated upon on the same day by the same surgeon, according to the study, published online in October 2009 in the European Journal of Ophthalmology. The mistake was noticed at the end of the day. “The 6 patients were followed up very closely every day during the first week,” Dr. Sakarya reported. “At postoperative day 1, slit-lamp findings included quiet anterior chamber, clear cornea without obvious edema, minimal Descemet stria, clear vitreous, no signs of toxic anterior segment syndrome, no pupil dilatation, intraocular pressure within normal range, no intraocular lens discoloration, no signs of iridocyclitis, and no cystoid macular edema.”

Examination from the first week to six months post-op showed that no significant change in these ocular findings occurred. “All the patients achieved 20/20 or better vision at the end of the first week,” Dr. Sakarya reported.

The case may have been a near miss in terms of potential adverse reactions. “In an in vitro study, dose-dependent toxicity of cefuroxime on cultured human corneal endothelial cells started at a concentration above 2.75 mg/mL,” Dr. Sakarya noted. Although patients received a higher dose than this of cefuroxime, the concentration quickly diminished for patients in this study. “In our cases, intracameral 3 mg/0.1 mL cefuroxime injection yields approximately 8.6 mg/mL to 15 mg/mL cefuroxime concentration in anterior chamber,” Dr. Sakarya reported. “Assuming an aqueous turnover rate of approximately 2 hours, these high initial antibiotic levels drop below 2.75 mg/mL concentration in 3 to 5 hours.”

This was not the first time that an erroneously high dose of intracameral antibiotics was used without adverse reaction. “[Another physician] erroneously injected 5 mg/0.1 mL vancomycin instead of 1 mg/0.1 mL concentration in 3 eyes and reported no adverse effect postoperatively,” Dr. Sakarya noted.

What caused the cefuroxime dilution mistake to begin with? “The boxes and the vials of 250 mg and 750 mg Zinnat [GlaxoSmithKline, Middlesex, U.K.] were similar,” Dr. Sakarya reported. “Strict precautions and clear communication between nurses and surgeons are important to prevent such a mistake in preparation of dilution. Precise labeling of every injectable solution is mandatory in the operation room.”

Zinnat was used to create the cefuroxime solution. John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va., still cautions that the use of intracameral cefuroxime is risky. “Although intracameral antibiotics are useful in preventing a small percentage of post-op endophthalmitis, the unfortunate fact is that we still don’t have a modicum of standard data to establish the safety of intracameral injections,” he said.

He suggested that cefuroxime could have a deleterious effect on retinal tissues or trabecular meshwork tissues. “There have not been well thought-out trials or animal models looking at subtle toxicity issues,” he said. “As a reminder, intravitreal Kenalog (triamcinolone, Bristol-Myers Squibb, New York), whose initial usage was extremely popular, resulted in a variety of toxicities after a detailed evaluation.” He also suggested that while this study found visual acuity remained favorable after the mistaken dosage was administered, the incident also “poignantly outlines the hazards of intracameral medication use in that a number of errors can occur with its administration and preparation.”

Editors’ note: Dr. Barry has no financial interests related to his comments. Dr. Sakarya has no financial interests related to his study. Dr. Sheppard has no financial interests related to his comments.

Contact information

Sheppard: 757-622-2200,

Exercising caution with prophylaxis Exercising caution with prophylaxis
Ophthalmology News - EyeWorld Magazine
283 110
216 173
True, 3